USPTO Patents Application 10687850

J

Europaisches Patentamt

© European Patent Office ® Publication number: 0 010 456

Office europeen des brevets A1

© EUROPEAN PATENT APPLICATION

@ Application number: 79302339.1 @ InL CI. 3 : B 01 L 3/00

' G 01 N 33/48

@ Date of filing: 25.10.79

@ Priority: 23.07.79 US 59924
25.10.78 US 954689

(43) Date of publication of application:
30.04.80 Bulletin 80/9

@ Designated Contracting States:
AT BE CH DE FR GB IT NL SE

(7?) Applicant: EASTMAN KODAK COMPANY
343 State Street
Rochester, New York 14650(US)

(72) Inventor: Columbus, Richard Lewis
Kodak Park

Rochester, New York(US)

(74) Representative: Trangmar, Leigh Alan et at
KODAK LIMITED P.O. Box 114 246 High Holborn
London WC1V 7EAIGB)

(5) Liquid transport device.

(£7) A device (10) that includes an ingress aperture (30) which
provides improved transport of a drop of liquid, from an
exterior surface (16) of the device to the device interior. Means
are provided at the intersection of the aperture sidewall (32)
and the exterior surface for urging a drop deposited thereon
to move into contact with the aperture sidewall and thus into
the aperture. In the disclosed embodiments such means are in
the form of interior corners (34).

<0

in
o

r-
O

O

FIG. I

Q.

Croydon Priming Company Ltd.

0010456

i

liquid transport device

This invention relates to the flow of liquid
through an aperture leading from a surface, the liquid
having arrived on the surface in the form of a drop.

5 In U.S. Patent Specification No. 3,690,836

there is disclosed a device for use in the study of
chemical and biological reactions and method of making
same. One embodiment therein disclosed includes an
exterior surface having an aperture extending from the
10 exterior surface to a zone within the device. This
zone is a capillary tube or chamber. The tube or
chamber is filled with liquid introduced through the
aperture. In this known device the ingress aperture
for introduction of liquid has a smooth, cylindrical

15 sidewall. Such an aperture has the disadvantage that
a drop of liquid which is not accurately placed on the
exterior surface, that is, it is placed with its
centre outside the sidewall of the aperture, tends to
stay outside the aperture rather than move into it.

20 It is only when the centre of the drop is deposited
well within the aperture that the surface tension of
the liquid drop forces .the drop into the aperture In
full contact with the sidewall. In particular this
has been a problem when the exterior surface is formed

25 of material which tends to be hydrophobic, that is,
that forms with the liquid a liquid-vapour contact
angle that is greater than 90°. For example certain
plastics materials are sufficiently hydrophobic that
drops of liquid such as blood serum are more likely to

30 remain on the exterior surface than to flow into the
aperture.

In accordance with the present invention there
is provided a liquid transport device having an exterior
surface, an aperture extending from the exterior surface
35 to a zone within the device, said zone having means for

2

0010456

10

transporting the liquid through a zone, characterized
in that at least the intersection of said exterior
surface and the bounding surface of the aperture
includes, at a predetermined location, means for
substantially urging a portion of a drop of liquid
deposited thereon to move into contact with the bounding

surface of- the aperture.

Such a device is particularly useful in
introducing liquid into a transport zone between two
opposed transport surfaces spaced apart a distance
effective to induce capillary flow of the liquid
between the transport surfaces.

Embodiments of the present invention will
now be described, by way of example, with reference to
15 the accompanying drawings in which:

Fig . i is an enlarged perspective view of a
device in accordance with the invention;

Fig. 2 is an elevational view in section
taken on the line 11-11 in Fig. 1, demonstrating the

20 operation of the device;

pig . 3 is a fragmentary, diagrammatic plan
view illustrating an effect achieved in a device in
accordance with the invention;

Fig. t is a plan view of a second embodiment

25 of the invention; and

Fig. 5 is a sectional view taken generally
along the plane of line V-V in Fig. 4.

The device and method of this invention is
described in connection with embodiments featuring the
30 capillary transport of biological liquids and par-
ticularly blood serum, between two opposed surfaces.
In addition, the device and method can be applied to
any liquid a drop of which is to be carried through an
ingress aperture from an exterior surface to a trans-
35 port means for transporting the liquid for any pur-
pose. For example, industrial liquids can be so
transported.

3

0010456

A device 10 constructed in accordance with
one embodiment of the invention comprises (see Fig. 1)
two members 12 and 14 having respective exterior surfaces
16 and l8 t and respective interior, opposed surfaces

5 20 and 22. The members 12, 14 have

boundary edge surfaces 2*. Surfaces 20 and 22 are
spaced apart a distance "x M (see Fig. 2) such that
capillary flow of liquid is induced between the
surfaces. In this manner the spaced-apart surfaces 20

10 and 22 define a transport zone 26 and act as means for
transporting introduced liquid between the surfaces.
As will be readily apparent, a range of values for "x"
is permissible, and the exact value depends upon the
liquid being transported.

15 Surfaces 20 and 22 can each be smooth, as

illustrated in Figs. 1 and 2, or provided with a
variety of surface configurations such as parallel
grooves, the grooves of one surface being aligned, or
at a positive angle, with respect to the grooves of
20 the other.

A preferred means for introducing a drop of
liquid into zone 26 is an aperture 30 extending from
surface 16 to surface 20, through member 12. The
aperture 30 comprises a sidewall 32 extending between the

25 surfaces 16 and 20. The preferred largest dimension of
aperture 30 in plan (for example the diameter of the
smallest circle which entirely encompasses the plan
form of the aperture), is one which is about equal to
the greatest diameter of the drop expected to be

30 received by the aperture 30. The drop diameter is
dictated by the volume and surface tension of the
drop. The volume of the drop should be adequate to
fill transport zone 26 to the extent desired. For
uses such as clinical analysis as herein described, a

35 convenient drop volume is about 10 ftl. Thus, since a
10 fil drop of serum having 70 dynes/cm surface tension

0010456

4

has a dimeter of about 0.26 cm, «-

through dimension, measured as described above is

preferably about 0.26 cm.

The intersection of suriace j-u «
32 is provided with means that encourage the selected
droP of liquid deposited or received in the plane of
surface 16 generally at aperture 30, to move into
ontact with the entire perimeter of ^^J 2 '
/ore specifically, sidewall 32 is shaped so as to
<\ „ Plurality of surfaces that intersect, at
L0 comprise a plurality predetermined
least at and adjacent surface lb, at preu
"cations to for* a plurality of Interior corners M.
La herein, "predetermined location" or "loca-
M„„ a " .reans locations deliberately chosen, and
15 rinses the present invention

apertures which inadvertently or accidentally have
perfections, such as microscopic comers in the
sidewall. such accidental '^"/^oP i»"
of P rcvidin e ^^T^r^.. -

P eri»eter. si, sidewall surfaces and s^auc.pr

25 surfaces Measured in^he dire ct on ; ^

the nerimeter of the sidewall 32) are sexe
a ha/e when viewed in plan. i.e. perpendicu ar^
-,c t>, a t ie a reeular hexagon, the pre
the surface l6, that is a regux

-rred .-^"^ (see 2) devlc e 10 is

30 pla ced in a drlp-displacin, tone ^
, i droo A of liquid such as blood serum,

: s- jt*. — - - r fa r

ro» drop or is touched off from a pendant
orientation during this step, corners 3« act to

5

0010456

centre the drop and urge it into contact with the
surfaces of sidewall 32. It then moves down into zone
26 and into contact with surface 22, where capillary
attraction further causes the liquid to spread through-
5 out zone 26, (see the arrows 36), so that the bounding
meniscus arrives at the position shown in broken
lines. Assuming sufficient volume in the drop, the
spreading ceases at edge surfaces 2k which define an
energy barrier to further capillary flow. Once the
10 drop of liquid is so distributed, a variety of pro-
cessing can be done to or with the liquid.

In order to ensure effective filling of the
aperture the drop should be applied to aperture 30 so
as to contact one of the corners. The effect is most
15 pronounced when the centre of gravity of the" drop is
positioned over the aperture 30, rather than over the
solid surface 16.

To vent air as the liquid advances within
zone 26, means are provided within the device, such as
20 the open space between members 12 and 1*1 along all or
a portion of any one of edge surfaces 2*J. Alter-
natively, a second aperture (not shown) can be formed
in either member 12 or Ik.

The corners of the aperture 30, at the surface
25 16 where the drop is first applied, seem to act as
centres of force which induce the drop to move into
contact with sidewall 32 along its entire perimeter or
circumference. That is, referring to Pig. 3, it is
believed that the centring force Fg of a drop A
30 applied at one of the corners 3^ is significantly
greater than the corresponding centring force P ]L or
F 2 that exists for a drop A 1 placed at any adjacent
location 38 or 39 spaced away from a corner 34, At least
one corner 34 is needed for the .effect. However, at
35 least three corners 3k are preferred, as in Fig. 3, to
ensure a greater likelihood that the drop A will be ir
contact with a corner 3k when it contacts surface 16*

6

0010456

For a predetermined largest dimension of the
aperture 30 calculated as described above, the greater
the number of corners that are created by the use of a
corresponding number of intersecting surfaces, then
5 the greater is the likelihood that the drop will

contact a corner. However, as the number of corners
is increased, so is the value of the interior angle of
each corner, until eventually the sidewall 32 ap-
proaches a smooth, curved surface" in shape wherein all
10 the centring forces are equal, and the effect is

lost. It has been found, therefore, that a preferred
number of corners is between three and about ten.
Highly preferred is six corners in a regular hexagon.

As a matter of practicality, the corners 3*
15 will have a slight radius of curvature. For the
corners to be effective, they each should have a
radius of curvature that is no larger than about 0.4 mm.

Although flat or planar surfaces are pre-
ferred between the corners, they can also be con-
20 tinuously curved as is shown, between the two lower

corners 3 1 * in Fig. 3.

Although the centring mechanism of the
comers is not fully understood, it is believed that
the effect is due to forces that apply to the compound

25 meniscus when the drop is located at a corner 3L As
is well known, a compound meniscus is one in which the
principal radii of curvature of the drop surface vary,
depending on the location taken on the surface of the
drop. If the drop Is properly located at a corner,

30 the compound meniscus forms a drop that extends

laterally farther out over the aperture than it does
when not located at a corner, and the weight of this
extension causes the drop to fall or otherwise move

• into contact with the perimeter of sidewall 32 and

3-5 then through the aperture 30. It may also be -that there
is»at the corner a greater tendency for the drop to

7

001045£

wet the sidewall than would occur In the absence of a
corner.

It will be readily appreciated that the
centring force of corners 34 is needed primarily at
5 the intersection of sidewall 32 and exterior surface
16. Thus, aperture 30 will function equally as well
if sidewall 32 is smoothed out, as it approaches
surface 20, to form a cylinder (not shown).

In addition, it will also be appreciated
10 that the presence of a capillary zone around the

downstream end of aperture 30 assists in drawing the
drop through aperture 30 and into the zone.

Members 12 and Ik can be formed from any
suitable material, such as plastics or metal.
15 In Pigs. 4 and 5, there is illustrated a

second embodiment of the device. This second embodi-
ment is one in which a transport chamber is formed for
radiometric analysis of an analyte of a biological
liquid such as blood. Parts similar to those pre-
20 viously described bear the same reference numeral but
with the distinguishing suffix "a" appended. Device
10a features a support member 14a (see Pig. 5), a cover
member 12a, a spacer member 50 used to adhere members
12a and l4a together, and a radiometrically detectable
25 test element 60 disposed on support 14a. The test
element 60 is spaced away from member 12a so that
there is a transport zone 26a between element 60 and
member 12a. The spacing between surface 20a and the
test element 60 is such as to produce a capillary
30 effect to induce the drop that enters through aperture
30a to spread throughout the zone 26a. Preferably,
the test element 60 abuts against the spacer member
50, and is held against member 14a by, for example,
adhesive.

35 Thus, the members 12a, l^a and 50 define a

capillary transport chamber containing the test
element 60 and having any convenient shape, such as a

8

001 045£

rectangular chamber when viewed In plan, as In Fig. 1 .

Any suitable Joining means can be employed
between members 12a and 50, and members 50 and 14a.
For example, a variety of adhesives can be used, or if
j all the members are thermoplastic, ultrasonic welding

or heat-sealing can be used.

Member 12a is provided with an access
- aperture 30a extending through the member from its
exterior surface l6a to zone 26a, disposed directly
10 above a portion of test element 60. At least that

portion of the aperture's sidewall 32a that intersects
with surface l6a is provided with corners 34a, as
described above. Preferably sidewall 32a is in the
cross-sectional shape of a regular hexagon. An
15 additional, cylindrically shaped, aperture 70 in
member 12a acts as a vent for expelled air.

A. viewing port 80 is optionally provided in
support member 14a, particularly when the latter
member is not itself transparent.
20 Test element 60 comprises an optional

transparent support 62, formed, for example of poly
(ethylene terephthalate) , and at least an absorbent
layer 64 disposed on support 62. Such layer can have
a variety of binder compositions, for example,
25 gelatin, cellulose acetate butyrate, polyvinyl alcohol,
agarose and the like, the degree of hydrophiliclty of
which depends upon the material selected. Gelatin is
particularly preferred as it acts as a wetting agent
to provide for uniform liquid flow through zone 26a.
30 support 62 can be omitted where adequate support for
layer 64 can be obtained from support member l4a.

Additional layers such as a layer 66 can be
disposed above layer 64 to provide a variety of
chemistries or functions, such as to provide, either
35 in layer 66 alone or together with layer 61, a reagent
composition. Filtering, registration and mordanting

9

001045£

functions can be provided also by such additional
layers, such as are described in U.S. Patent Speci-
fication No. 4,042,335. Thus, layer 66 .can comprise a
reagent, such as an enzyme, and a binder of the same
5 type as is used for layer 64.

As used herein, "reagent" in "reagent

composition" means a material that is capable of
interaction with an analyte, a precursor of an analyte,
a decomposition product of an analyte, or an inter-
10 mediate. Thus, one of the reagents can be a pre-
formed, radiometrically detectable species that is
caused by the analyte of choice to move out of a
radiometrically opaque portion or layer of the element,
such as layer 66, into a radiometrically transparent
15 portion or layer, such as a registration layer.

The noted interaction between the reagents
of the reagent composition and the analyte is there-
fore meant to refer to chemical reaction, catalytic
activity as in the formation of an enzyme-substrate
20 complex, or any other form of chemical or physical

interaction, including physical displacement, that car.
produce ultimately a radiometrically detectable signal
in the element 60. As is well known, radiometric
detection includes both colorimetric and fluorimetric
25 detection, depending upon the indicator reagent

selected for the assay. The assay of the element is
designed to produce a signal that is proportional to
the amount of analyte that is present.

A wide variety of radiometric assays can be
30 provided by element 60. Preferably, the assays are
all oxygen-independent, as the flow of blood or blood
serum into zone 26a tends to seal off element 60 from
any additional oxygen. Typical analytes which can be
tested include BUN, total protein, bilirubin and the
35 like. The necessary reagents and binder or vehicle
compositions for the layers of element 60, such as

10

001045£

layers 6*1 and 66, for these analytes can be those
described in, respectively, U.S. Patent Specification
Nos. 4,066,403, M32,528 and 4,069,016 or 4,069,017.

Quantitative detection of the change pro-
5 duced in element 60 by reason of the analyte of the
test element is preferably made by scanning the
element through port 80 with a photometer or fluori-
meter. A variety of such instruments can be used, for
example the radiometer disclosed in German 0LS
10 2,755,334, or the photometer described in U.S. Patent
Specification No. 4,119,381. ■

The following is an illustrative example of
the device shown in Figs. 4 and 5-
Example

15 Members 12a and l4a are formed from poly-

styrene of a thickness 0.127 and 0.254 mm, respect-
ively. Member 50 is steel of a thickness 0.38 mm.
The three members are* sealed together by adhesives
such as polybutyl acrylate adhesive obtainable from

20 Franklin Chemical under the trademark "Covinax".
Apertures 30a and 70 in member 12a are about 8 mm
apart on centre. The outside diameter of the hexagon
form of aperture 30a is about 2.6 mm. View port 80 is
about. 5 mm in diameter. The capillary spacing between

25 test element 60 and member 12a is about 0.05 mm and
the width of element 60 is about 11.5 mm.

For a test element 60 designed to detect
total protein in a 10 M l drop of blood serum, the
following sequential layers are used:

11

001 045£

Composition
Gelatin-subbed

poly (ethylene tere-

phthalate)
poly(acrylamide-co-N-

vinyl-2-pyrrolidone
CuSCy5H 2 0
Li OH

tartaric acid

Amount
175 microns
thick

16.0 g/m 2

10.8 g/m*
8.0 g/m 2

12

001 0456;

claims

! A liquid transport device having an
exterior surface, an aperture extending from the
exterior surface to a zone within the device, said
5 zone having means for transporting the liquid through
' a zone, characterized in that at least the inter-
section of said exterior surface and the bounding
surface of the aperture includes, at a predetermined
location, means for substantially urging a portion of
10 a drop of liquid deposited thereon to move into
contact with the bounding surface of the aperture.

2i A device according to claim 1, char-
acterized in that said urging means comprises a
surface configuration capable of forming a compound
15 meniscus on a contacting liquid drop.

3> A device according to claim 1 or 2,
characterized in that said urging means comprises at least
one interior corner in the bounding surface of the
aperture at at least its intersection with said extern
20 surface.

1] a device according to claim 3, char-
acterized in that there are from three to ten similar
interior corners at predetermined spaced-apart loca-
tions at at least said intersection.

5 A device according to claim 1, char-
acterized in that there are six of said

6 A device according to claim 5, char-
acterized in that the bounding surface of the aperture
conforms to a regular hexagon at least adjacent the

50 exterior surface.

7 A device according to any one of the
preceding claims/characterized in that the trans-
porting means in said zone includes two opposed
surfaces of the zone spaced apart a distance such as

35. to cause capillarity.

13

001 045£

8. A device according to claim 7, char-
acterized in that at least one of said two spaced-
apart opposed surfaces includes an absorbent layer
containing at least one reagent capable of producing a
5 radiometrically detectable signal when contacted by
the liquid of the drop.

9. A device according to claim 3 or any
one of claims 4 to 8 when appendant directly or
indirectly to claim 3, characterized in that the
10 corner or each of the corners extends throughout the
length of the bounding surface of the aperture, from
the exterior surface to the zone.

2/2

0010456

FIG. 4

tOo

30o 32o

70 12a

FIG. 5

I

J)

Alll European Patent

yj)) Office

EUROPEAN SEARCH REPORT

Application nQn^jr^ ^

EP 79 30 2339

Category

DOCUMENTS CONSIDERED TO BE RELEVANT

Citation of document with Indication, where appropriate, ol relevant
passages

US - A - 3 690 836 (J. BUISSIERE)

* Whole document *

FR - A - 1 444 146 ( PR0M0VEO )

* Whole document *

US - A - 3 565 537 (J. FIELDING)

* Whole document *

US - A - 3 992 158 (E.P. PRZYBYLO-

wlczl

* Whole document *

Relevant
to claim

The present search report has been drawn up for aft claims

B

3 01 L 3/00
3 01 H 33/48
21/29

CLASSIFICATION OF THE
APPLICATION (Int. CI. ')

01 L 3/00
01 H 33/48

TECHNICAL FIELDS
SEARCHED (IntCI. 3>

CATEGORY OF
CITED DOCUMENTS

X: particularly relevant
A: technologies! background
O: non-written disclosure
P: intermediate document
T: theory or principle underlying

the Invention
E; conflicting application
D: document cited m the

application
L: citation for other reasons

a: member of the same patent
family,

corresponding document

Place of search

The Hague

Date of completion of the search

31-01-1980

Examiner

DUCHATELLIER

EPO Form 1503.1 06.78

I

THIS PAGI BLANK (ubpto)